Brain-derived Neurotrophic Factor Attenuates Radiation-induced Dendritic Growth Impairment Of Newborn Neurons In Hippocampus

Objective To investigate the effects of low dose radiation on dendritic growth of newborn neurons in young rat hippocampus and the protective function of exogenously applied BDNF.Materials and Methods 1.One-month-old male rats were randomized into radiation group and sham control group. Radiation group received whole brain irradiation at a single dose of 2Gy. Retrovirus expressing green fluorescent protein(GFP) was used to label newborn neurons in the hippocampus through stereotaxic intracranial infusion. Immunofluorescence assays were performed to detect dendritic architecture alterations induced by irradiation at different time points. 2. One-month-old male rats were randomized into 2Gy+BDNF group and 2Gy+ saline group. All animals received whole brain irradiation at a single dose of 2Gy. Retrovirus expressing green fluorescent protein(GFP) was used to label newborn neurons in the hippocampus through stereotaxic intracranial infusion. Animals were implanted with stainless guide cannulas at the end of the retrovirus stereotaxic injection surgery. The treatment of BDNF was applied for 4 d after irradiation. Immunofluorescence assays were performed to detect dendritic architecture alterations at different time points.Results Significant reductions of total dendritic length and length of the longest dendrite at 2 weeks and 4 weeks after exposure to single dose of 2 Gy whole-brain irradiation(2 w, total dendritic length, P<0.01;2 w, length of the longest dendrite, P<0.05; 4 w,total dendritic length, P<0.01; 4 w, length of the longest dendrite, P<0.001). A reduction in the number of dendritic branching points was found at 2 weeks after retrovirus injection(P<0.05). At 4 weeks and 8 weeks post irradiation, the amount of new born neurons in the hippocampal dentate gyrus was significantly decreased(4 w, P <0.05; 8 w, P <0.01).BDNF treatment caused a significant increase(P< 0.05)of dendritic branching points at 2 weeks. At 4 weeks after retrovirus injection, total dendritic length had greatly increased(P<0.001) in response to BDNF treatment after 2Gy radiation.Conclusion Neuronal dendrites are the anatomical bases for neural signaling transmission. Ionizing radiation can significantly inhibit dendritic growth of newborn neurons in juvenile rat hippocampal dentate gyrus. The complexity of newborn neurons dendritic(dendritic length, branching points, etc.) was significantly reduced after irradiation, which may influence the formation of synaptic connections between neurons. Extraneous BDNF may serve as an effective treatment to reverse this impairment.